Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

Abstract

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema.

A Review of Filovirus Work and Facilities at The Defence Science and Technology Laboratory Porton Down

“…Marburg virus infection resulted in a consistent temperature profile with fever evident on the 5 th day post infection, and the average time to death was 9 days. Inhaled doses of as low as 4 TCID 50 units were lethal, and the pathogenesis of disease, blood parameters and histology was consistent with what is seen in other non-human primates, and also similar to the limited information gathered from human cases of filovirus infection [13]. The marmoset model offers both the advantages of a small animal model (greater capacity, quicker throughput, safer handling) and the advantages of a primate model (similarities to human disease) and so will be a useful tool in the testing and licencing of medical countermeasures against filovirus infection.…”

“…Dstl has also developed a non-human primate model of aerosolised Marburg virus infection, in the common marmoset ( Callithrix jacchus ) [13], and work is underway to develop models of Ebola virus infection by both the aerosol and an injected route to model both natural and un-natural exposure methods. Marburg virus infection resulted in a consistent temperature profile with fever evident on the 5 th day post infection, and the average time to death was 9 days.…”

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

“…Although hamsters were used following the original 1967 outbreak of MARV to characterize general features of MARV pathogenesis24, our work here expands upon this initial work and offers a more rigorous analysis along with important and novel insights that have not been described until now. Indeed, our hamster model accurately recapitulated all the critical clinical hallmarks observed in humans and NHPs infected with MARV68102223252627282930, making it one of the most accurate small animal disease models developed for MHF to date.…”

Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses

“…Only one description was associated with diffuse congestion, haemorrhage and suppurative pneumonia, but the patient had a bacterial co‐infection . Experimental studies show variable lesions, which range from oedema, focal haemorrhage and necrosis in non‐human primates to pneumonia in pigs .…”